Value of therapeutic drug monitoring of endoxifen in Egyptian premenopausal patients with breast cancer given tamoxifen adjuvant therapy: A pilot study.

BACKGROUND: The complex metabolic profile of tamoxifen anticancer drug and polymorphism in its metabolizing enzymes particularly CYP2D6 contribute to the high-observed inter-individual variability in its main active metabolite endoxifen. Therapeutic drug monitoring of endoxifen may play a key role in optimizing tamoxifen therapy, and control of both adverse effects and cancer recurrence. This pilot study aims to assess the clinical benefits of applying endoxifen measurement during tamoxifen therapy in patients with breast cancer. METHODS: Adult premenopausal breast cancer patients ≥ 18 years who received tamoxifen at a fixed dose of 20 mg daily were included. The primary endpoint was to identify the inter-subject variability in serum concentration of the drug and its metabolites especially endoxifen, through fixation of the tamoxifen dose. The secondary endpoint was to check the correlation between endoxifen metabolite concentration and the development of tamoxifen's adverse effects and cancer recurrence. RESULTS: Sixty patients were included in the study with a mean age of 38.4 ± 0.6 years (range: 26-50). The mean concentration of tamoxifen and endoxifen was 181 ± 9.6 ng/mL and 31.49 ng/mL, respectively. The inter-individual variability in concentrations for the drug and its active metabolite as estimated by the coefficient of variation percentage was in 41% and 31%, respectively. Cancer recurrence was observed in a group of patients (n = 16) with an average endoxifen level of 24.48 ng/mL. Another group of patients (n = 25) developed different tamoxifen adverse effects including hot flashes, vaginal bleeding, endometrial thickness, and ovarian cysts with the average endoxifen level of 38.61 ng/mL. The rest of the patients (n = 19) who responded smoothly to the drug with no complications had an average endoxifen level of 31.37 ng/mL. Analysis of variance test showed a significant difference in endoxifen levels between the three groups (p = 0.002). CONCLUSION: The measurement of the endoxifen active metabolite of tamoxifen in breast cancer patients can help dose optimization in light of the observed wide inter-individual variability in drug fixed-dose related concentration of the metabolite. Monitoring of serum concentration of endoxifen can help to reveal, reduce and control tamoxifen's adverse effects and cancer recurrence.

Spastic Paraplegia 20 and Serine/Threonine Protein Kinase 31 Expression for the Detection of Colorectal Cancer.

BACKGROUND/AIMS: Genetic alterations, including changes in the expression of spastic paraplegia 20 (SPG20) and serine/threonine protein kinase 31 (STK31), may play an important role in the carcinogenesis of colorectal cancer (CRC). Identification of such changes is suitable for the recognition of tumors at an early stage, which would significantly improve patient survival. While recent studies have identified that SPG20 and STK31 expression levels increase in CRC tissues, their use as a biomarker is yet to be investigated. Our aim was to determine whether circulating SPG20 and STK31 mRNAlevels could help distinguish between patients with CRC and healthy individuals. Additionally, we aimed to analyze the correlation between SPG20 and STK31 expression patterns and the tumor stage in patients with CRC. METHODS: Venous blood samples from 50 patients with CRC and 50 healthy controls were used. RNA extraction was performed, and the mRNA expression of SPG20 and STK31 was determined using RT-qPCR. RESULTS: STK31 and SPG20 mRNA levels were significantly upregulated in patients compared to those in controls. There was a strong positive correlation between the expression of the two potential tumor biomarkers, STK31 and SPG20 (R=0.636, p=0.000). However, there was no significant relationship between the expression of STK31 or SPG20 and patient data, including demographic, clinical, pathological, and laboratory data. Additionally, there was a significant correlation between the expression level of STK31, but not SPG20, and patient disease-free survival (DFS) and overall survival (OS). CONCLUSION: Circulating mRNA levels of SPG20 and STK31 could be used as ideal noninvasive biomarkers for early diagnosis of CRC. They could assist the oncologist in recommending appropriate management strategies for individual patients.

Acidic Exo-Polysaccharide Obtained from Bacillus sp. NRC5 Attenuates Testosterone-DMBA-Induced Prostate Cancer in Rats via Inhibition of 5 α-Reductase and Na+/K+ ATPase Activity Mechanisms.

Bacillus sp. NRC5 is a new strain that grows in Egyptian beaches. This strain produces acidic exo-polysaccharide that have excellent antioxidant, anti-inflammatory and anti-tumor properties. The current study aimed to introduce a new natural product feasible for prostate cancer therapies. The anti-prostate cancer of acidic exo-polysaccharide produced from marine Bacillus sp. NRC5 (EBPS) was determined using 7,12-dimethylbenz-(a)-anthracene; DMBA-induced prostate cancer in male Sprague Dawley rats. Rats were subcutaneously injected with testosterone (3 mg/kg/day for 3 months) and a single dose of DMBA (65 mg/kg) for induction of prostate cancer. EBPS was administrated orally at dose 200 mg/kg/day for 3 months. To study protective effect of EBPS, animals received EBPS before cancer induction, meanwhile in therapeutic effect animals received EBPS after cancer induction. EBPS debug oxidative stress and inflammatory conditions associated with prostate cancer. EBPS either protective or therapeutic material considerably reduced cancer growth rate-limiting enzyme-i.e., 5-α-reductase (46.89 ± 1.72 and 44.86 ± 2.56 µg Eq/mL) and Na+/K+ ATPase (0.44 ± 0.03 and 0.42 ± 0.02 µg Eq/mL), compared to cancer control (69.68 ± 3.46 µg Eq/mL). In addition, both cancer biomarkers-i.e., prostate-specific antigen and carcinoembryonic antigen were significantly lowered as evidence of the ability of EBPS to protect and treat prostate cancer in chemically induced rats. EBPS showed protective and therapeutic efficacy on testosterone-DMBA-induced prostate cancer rats with a good safety margin. This study may go to clinical trials after a repeated study on another type of small experimental animal, their offspring, and one big experimental animal.

The risk of Parkinson's disease in women who underwent hysterectomy before the age of menopause.

Introduction: Parkinson's disease (PD) is the second most common neurodegenerative aging disorder. Oestrogen has been shown to have a neuroprotective effect against PD in animal models.This study aimed to detect the risk of PD in women who underwent hysterectomy before the age of menopause. Material and methods: Seventy-six women with PD (study group) were recruited for this retrospective study and compared to 80 controls. Collected data included the education level, smoking, age of menopause, type of menopause (natural or surgical), past surgical history of hysterectomy, type of hysterectomy (hysterectomy only or hysterectomy with oophorectomy [unilateral, bilateral]), and use of postmenopausal oestrogen replacement therapy. The collected data were analysed to detect the risk of PD in women who underwent hysterectomy before the age of menopause. Results: The odds ratio (OR) and relative risk (RR) of PD was significantly higher after surgical menopause in the study group (30 [39.5%]) compared to controls (17 [21.25%]), (OR 2.4 [95% CI: 1.19-4.8]; p = 0.01, RR 1.9 [95% CI: 1.12-3.1]; p = 0.016). In addition, the OR and RR of PD was significantly higher after bilateral oophorectomy in the study group (19 [25%]) compared to controls (8 [10%]), (OR 3.0 [95% CI: 1.22-7.4]; p = 0.016, RR 2.5 [95% CI: 1.16-5.4]; p = 0.01). Conclusions: The risk of PD increased in women who underwent hysterectomy and bilateral oophorectomy before the age of menopause, and the risk of PD did not increase whether the menopause, either natural or surgical, occurred before 48 years of age.

Production, structural and biochemical characterization relevant to antitumor property of acidic exopolysaccharide produced from Bacillus sp. NRC5.

This study targeted the production of exopolysaccharide from Bacillus sp. NRC5 grown in Egyptian seawater to use it as natural antitumor therapy. The biological activities of selected exopolysaccharide (BEPS) as an antioxidant, anti-inflammatory and anticancer have been studied. BEPS was evaluated as an anti-inflammatory in vitro against cyclooxygenase (COX-1 and COX-2) and evaluated as an anticancer on human breast and prostate cancer cell lines (MCF-7 and PC3). In addition, BEPS antitumor activity was tested against the Ehrlich Ascites Carcinoma (EAC) model. The BEPS presented potent antioxidant activities, consisted of glucose, mannose, and mannuronic acid in a molar ratio of 1.0:1.7:0.8 with a molecular weight of 3.59 × 105 g/mol. BEPS showed a promising COX-2 inhibitory effect in comparison with the reference drug celecoxib. BEPS appeared efficient anticancer property, where it killed 64.20 and 70.20% of MCF-7 and PC3 cells at 100 µg/ml, respectively (IC50, 76.70, and 70.40 µg/ml, respectively). BEPS exhibited antitumor ability as it prolonged the lifespan of mice to reach 75 days instead of 20 days in the tumor control, reduced viable cancer cells count, tumor volume and weight, modulated blood components, and white blood cells differentiation. BEPS produced from Bacillus sp. NRC5 showed its antioxidant and anti-inflammatory abilities and antitumor abilities, which may all be attributed to its unique composition containing sulfated moieties and uronic acids.

Ischemic Pressure vs Postisometric Relaxation for Treatment of Rhomboid Latent Myofascial Trigger Points: A Randomized, Blinded Clinical Trial.

OBJECTIVE: The purpose of this study was to investigate the effects of ischemic pressure (IP) vs postisometric relaxation (PIR) on rhomboid-muscle latent trigger points (LTrPs). METHODS: Forty-five participants with rhomboid-muscle LTrPs were randomly assigned into 3 groups and received 3 weeks of treatment-group A: IP and traditional treatment (infrared radiation, ultrasonic therapy, and transcutaneous electrical nerve stimulation); group B: PIR and traditional treatment; and group C: traditional treatment. Shoulder pain and disability, neck pain and disability, and pressure pain threshold (PPT) of 3 points on each side were measured before and after treatment. RESULTS: Multivariate analysis of variance indicated a statistically significant Group × Time interaction (P = .005). The PPT for the right lower point was increased in group A more than in groups B or C. Neck pain was reduced in group B more than in group C. Moreover, shoulder and neck disability were reduced in both groups A and B more than in group C. The PPTs of the left lower and middle points were increased in group B compared with groups A and C. The PPT of the left upper point was increased in group A more than in group C. There were significant changes in all outcomes in the 2 experimental groups (P < .05). No changes were found in the control group except in pain intensity, shoulder disability, and PPT of the left lower point. CONCLUSION: This study found that IP may be more effective than PIR regarding PPT, but both techniques showed changes in the treatment of rhomboid-muscle LTrPs.

Efficacy of Kinesio Taping and Postural Correction Exercises on Levator Scapula Electromyographic Activities in Mechanical Cervical Dysfunction: A Randomized Blinded Clinical Trial.

OBJECTIVE: Mechanical neck dysfunction (MND) is a major health burden. Although postural correction exercises (PCEs) are commonly used for its treatment, efficacy of Kinesio Taping (KT) has received considerable attention. This study was conducted to determine the effect of KT and PCEs on levator scapula (LS) electromyography. METHODS: Ninety-one patients with MND were randomly assigned into 1 of 3 groups that received 4 weeks' treatment: group A, KT; group B, PCE; and group C, both interventions. Neck pain, LS root mean square (RMS), and median frequency (MDF) were measured pretreatment and post-treatment with the Numerical Pain Rating Scale and surface electromyography, respectively, by an assessor blinded to the patients' allocation. RESULTS: Multivariate analysis of variance indicates a statistically significant group-by-time interaction (P = .000). Pain intensity was significantly reduced in group C more than in group B (P = .001). Mean values of RMS were significantly reduced in group C compared to both group A (P = .001) and group B (P = .022), whereas MDF was significantly increased in group C compared to either group A (P = .00) or group B (P = .026), and in group B compared to group A (P = 0.26). A paired t test revealed that there was a significant decrease in pain and RMS, and a significant increase in MDF in all groups (P < .01). CONCLUSION: Application of both KT and PCE combined can significantly reduce neck pain and normalize LS activities in patients with MND more than the application of either intervention.

Long-term effects of pulsed high-intensity laser therapy in the treatment of post-burn pruritus: a double-blind, placebo-controlled, randomized study.

We assessed the long-term effects of pulsed high-intensity laser therapy (HILT) in post-burn pruritus treatment. A total of 49 adult burn patients with mean age of 31.53 ± 10.14 years participated, with 24 patients randomly assigned to the active laser group (ALG) and 25 in the placebo laser group (PLG). The ALG received HILT three times per week for 6 weeks, while the PLG received placebo HILT. Both groups received 10-mg cetirizine tablets twice daily and 10 mg at bedtime. All patients were advised to massage their burn scars with coconut oil for 5 min four times daily. The outcomes measured were the itch severity scale (ISS), impairment of pruritus-related quality of life (QoL), pain level by the visual analog scale (VAS), hand grip strength by handheld dynamometer, and daily cetirizine intake. Repeated-measures ANOVA was used to compare the baseline and post-treatment measurements and after 12 weeks of follow-up. Statistical significance was set at P < 0.05. ISS decreased significantly in the ALG after 6 weeks of treatment and after 12 weeks of follow-up compared with the PLG. The QoL results showed a significant improvement in the ALG compared with the PLG, which continued after 12 weeks. VAS results significantly decrease, hand grip strength significantly improved, and cetirizine intake significantly decreased post-treatment in the ALG relative to the PLG. HILT combined with cetirizine seems more effective in patients with post-burn pruritus than a placebo laser procedure with cetirizine.

Sesquiterpene Lactones from Cynara cornigera: Acetyl Cholinesterase Inhibition and In Silico Ligand Docking.

Wild artichoke (Cynara cornigera), a thistle-like perennial belonging to the Asteraceae family, is native to the Mediterranean region, northwestern Africa, and the Canary Islands. While the pleasant, albeit bitter, taste of the leaves and flowers is attributed to the sesquiterpene lactones cynaropicrin and cynarin, a comprehensive phytochemical investigation still needs to be reported. In this study seven sesquiterpene lactones were isolated from an aqueous methanol plant extract, including a new halogenated metabolite (1), the naturally isolated compound sibthorpine (2), and five metabolites isolated for the first time from C. cornigera. Structures were established by spectroscopic methods, including HREIMS, (1 )H, (13 )C, DEPT, (1 )H-(1 )H COSY, HMQC, and HMBC-NMR experiments as well as by X-ray analysis. The isolated bioactive nutrients were analyzed for their antioxidant and metal chelating activity. Compound 1 exhibited a potent metal chelating activity as well as a high antioxidant capacity. Moreover, select compounds were effective as acetyl cholinesterase inhibitors presenting the possibility for such compounds to be examined for anti-neurodegenerative activity. A computational pharmacophore elucidation and docking study was performed to estimate the pharmacophoric features and binding conformation of isolated compounds in the acetyl cholinesterase active site.

Evaluation of the Role of Circulating Long Non-Coding RNA H19 as a Promising Novel Biomarker in Plasma of Patients with Gastric Cancer.

BACKGROUND: H19 is one of the long non-coding RNAs (LncRNA) that is related to the progression of many diseases including cancers. This work was carried out to study the level of the long non-coding RNA; H19, in plasma of patients with gastric cancer (GC) and to assess its significance in their clinical management. METHODS: Sixty-two participants were enrolled in the present study. The first group included 32 GC patients. The second group was formed of 30 age and sex matched healthy volunteers serving as a control group. Plasma samples were used to assess H19 gene expression using real-time quantitative PCR technique. RESULTS: H19 expression was up-regulated and closely related to TNM cancer stages in GC patients. Using Receiver Operating Characteristic (ROC) curve analysis, a cutoff level of 0.5 was set for H19 expression to diagnose GC cases achieving a sensitivity of 68.75%, specificity of 56.67%, positive predictive value (PPV) 62.86% and negative predictive value (NPV) 62.96% with an area under the curve (AUC) of 72.4%. Combined use of Carcinoembryonic Antigen (CEA) and H19 level in GC diagnosis was evaluated using ROC curve revealing improvement in performance with an area under the curve of 80.4%. CONCLUSIONS: Up-regulation of H19 is closely associated with gastric cancer displaying progressive up-regulation in advanced stages of the disease implementing its role as a potential non-invasive diagnostic biomarker in gastric cancer and as a novel tool in gastric cancer management with better performance achieved on using both CEA and H19 simultaneously.

Prognostic value of regulatory T cells in newly diagnosed chronic myeloid leukemia patients.

BACKGROUND: Chronic myeloid leukemia (CML) is a clonal disease, characterized by a reciprocal t(9, 22) that results in a chimeric BCR/ABL fusion gene. Regulatory T cells (Tregs) constitute the main cell population that enables cancer cells to evade immune surveillance. OBJECTIVE: The purpose of our study was to investigate the level of Tregs in newly diagnosed CML patients and to correlate it with the patients' clinical, laboratory and molecular data. We also aimed to assess the effect of treatment using tyrosine kinase inhibitor (TKI) on Treg levels. METHODS: Tregs were characterized and quantified by flow cytometry in 63 newly diagnosed CML patients and 40 healthy controls. TKI was used in 45 patients with chronic phase CML, and the response to therapy was correlated with baseline Treg levels. RESULTS: The percentages of Tregs were significantly increased in CML patients compared to the controls. Treg numbers were significantly lower in patients with chronic phase CML versus the accelerated and blast phases, and were significantly lower in patients with complete molecular remission (CMR) compared to those patients without CMR. CONCLUSION: Tregs may play a role in the maintenance of CML. Moreover, the decrease of their levels in patients with CMR suggests that Tregs might have a clinical value in evaluating the effects of therapy.

Effect of anti-gravity treadmill (Alter G) training on gait characteristics and postural stability in adult with healed burns: A single blinded randomized controlled trial.

BACKGROUND: Burns constitute one of the foremost contributors to premature mortality and morbidity, and the recovery process from burn injuries is characterized by its intricate and protracted nature. OBJECTIVE: The principal aim of this study was to assess the influence of an anti-gravity treadmill (Alter G) training program on both gait characteristics and postural stability indices (PSI) in adult individuals who have recovered from burns. DESIGN: This study followed a single-blind, randomized, controlled design. METHODS: A total of 45 adults, aged 18-35 years, with healed lower extremity burns that were circumferential and encompassed 35-50% of their total body surface area (TBSA) were randomly allocated to either the anti-gravity treadmill (Alter G) Training group (n = 22) or the traditional physical therapy program (TPTP) group (n=23). The TPTP group received conventional physical therapy, while the anti-gravity treadmill (Alter G) training group engaged in anti-gravity treadmill exercises alongside the traditional physical therapy program. The primary outcome measures, evaluated at both baseline and the conclusion of the 12-week intervention, included gait characteristics assessed using the GAITRite system and PSI measured by the Biodex Balance System (BBS). RESULTS: The anti-gravity treadmill (Alter G) training group exhibited significantly greater enhancements than the TPTP group in terms of mean values and percentage changes in gait characteristics and PSI. Specifically, the percentage changes for the Alter G group were as follows: stride length (20.57%), step time (22.58%), step length (20.47%), velocity (15.67%), cadence (23.28%), and double support time (29.03%). In contrast, the TPTP group's percentage changes were: 6.73%, 8.19%, 7.65%, 7.75%, 8.89%, and 9.37%, respectively. Concerning PSI, the Alter G group exhibited percentage changes of 55.17% for the medio-lateral stability index (MLI), 48.21% for antero-posterior stability index (API), and 48.48% for the overall stability index (OSI). The TPTP group's corresponding percentage changes were 20%, 14.03%, and 16.41%. CONCLUSIONS: The amalgamation of anti-gravity treadmill training with the traditional physical therapy program yields greater efficacy than TPTP in isolation. Consequently, the findings underscore the efficiency of anti-gravity treadmill (Alter G) Training as a valuable tool for rehabilitating patients with burn injuries.

Anti-Alzheimer's Potency of Rich Phenylethanoid Glycosides Extract from Marrubium vulgare L.: In Vitro and In Silico Studies.

BACKGROUND/OBJECTIVES: Marrubium vulgare L. (M. vulgare), the white horehound, is well known for treating inflammation-related diseases. METHODS: In this context, we investigated the efficacy of M. vulgare ingredients in treating Alzheimer's disease using various in vitro and in silico antioxidant, anti-inflammatory, anti-cholinesterase, and anti-tyrosinase mechanisms. RESULTS: In our results, sixty-one components were tentatively identified using gas and liquid chromatography (GC-MS and LC-MSn) and categorized as hydrocarbons, fatty acids, and polyphenolics. The extract inhibited linoleic oxidation with an IC50 value of 114.72 µg/mL, captured iron (Fe2+) ions with an IC50 value of 164.19 µg/mL, and displayed reducing power. In addition, the extract showed radical-scavenging ability towards DPPH•, NO•, ABTS•+, and H2O2 assays compared to L-ascorbic acid and butylated hydroxytoluene. The DPPH• was scavenged by 77.62% at 100 µg/mL, and NO•, ABTS•+, and H2O2 were scavenged with IC50 values of 531.66, 117.51, and 143.10 µg/mL, respectively. M. vulgare also exhibited discriminating anti-inflammatory potency against cyclooxygenase (COX-2) with IC50 values of 619.15 µg/mL compared to celecoxib (p > 0.05). Notably, three Alzheimer's biomarkers, acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and tyrosinase were significantly inhibited. The molecular docking study supposed that the phenylethanoid glycosides of samioside and forsythoside B inhibited AChE and tyrosinase enzymes with low binding affinities of -9.969 and -8.804 kcal/mol, respectively. Marruboside was a proper inhibitor of COX and BChE enzymes with a binding score of -10.218 and -10.306 kcal/mol, respectively. CONCLUSIONS: M. vulgare extract showed significant inhibitory actions, which suggest that it could have a promising potential as an anti-Alzheimer agent.

Functional outcomes of accelerated rehabilitation protocol for anterior cruciate ligament reconstruction in amateur athletes: a randomized clinical trial.

BACKGROUND: Anterior cruciate ligament (ACL) rupture is the most common knee injury among athletes, and can result in long-term complications and career-ending conditions for sportspeople. There is no consensus in the literature on the effectiveness of rehabilitation after ACL reconstruction, or the best protocol to follow for functional outcome improvement. OBJECTIVE: To determine the impact of an accelerated rehabilitation protocol on knee functional outcomes in amateur athletes with anterior cruciate ligament reconstruction (ACLR). DESIGN: Two-arm, parallel-group randomized comparative design. PATIENTS: A total of 100 amateur male athletes (mean age 22.01 ± 1.79 years) with ACLR were randomly divided into experimental and control groups (n = 50/group). METHODS: An accelerated rehabilitation protocol and a conventional rehabilitation protocol were used for the experimental group. In contrast, only the conventional rehabilitation protocol was used for the control group. The rehabilitation was delivered in 5 weekly sessions for 22 weeks. The primary outcome measure, knee pain, was measured using a visual analogue scale (VAS). Extensive test batteries, for hop tests, Knee Injury and Osteoarthritis Outcome Score (KOOS), and knee effusion, were measured, aiming to add more objective criteria to determine functional performance. RESULTS: Both groups (n = 50/group) were well-matched (p = 0.816), with insignificant differences in their demographic characteristics (p > 0.05). A multivariate analysis of variance (MANOVA) test showed no significant difference between the 2 groups (p = 0.781) at baseline. A 2-way MANOVA (2 × 2 MANOVA) of within- and between-group variations indicated overall significant treatment, time, and treatment × time interaction effects (p < 0.001) in favour of the accelerated rehabilitation group. CONCLUSION: The accelerated rehabilitation protocol was more effective in improving functional outcomes than a conventional rehabilitation protocol in amateur athletes with ACLR.

Long non-coding RNA (lncRNA) PVT1 in drug resistance of cancers: Focus on pathological mechanisms.

According to estimates, cancer will be the leading cause of death globally in 2022, accounting for 9.6 million deaths. At present, the three main therapeutic modalities utilized to treat cancer are radiation therapy, chemotherapy, and surgery. However, during treatment, tumor cells resistant to chemotherapy may arise. Drug resistance remains a major oppose since it often leads to therapeutic failure. Furthermore, the term "acquired drug resistance" describes the situation where tumor cells already display drug resistance before undergoing chemotherapy. However, little is still known about the basic mechanisms underlying chemotherapy-induced drug resistance. The development of new technologies and bioinformatics has led to the discovery of additional genes associated with drug resistance. Long noncoding RNA plasmacytoma variant translocation 1 (PVT1) has been linked to an increased risk of cancer, according to a growing body of research. Apart from biological functions associated with cell division, development, pluripotency, and cell cycle, lncRNA PVT1 contributes significantly to the regulation of various aspects of genome function, such as transcription, splicing, and epigenetics. The article will address the mechanism by which lncRNA PVT1 influences drug resistance in cancer cells.

Accuracy of international guidelines for identifying significant fibrosis in hepatitis B e antigen--negative patients with chronic hepatitis.

BACKGROUND & AIMS: Differing threshold levels of hepatitis B virus (HBV) DNA and alanine aminotransferase (ALT) are recommended by international guidelines for commencement of antiviral therapy. These guidelines advocate therapy for patients with significant fibrosis (METAVIR score ≥F2); we assessed the accuracy of these guideline-defined thresholds in identifying patients with ≥F2 fibrosis. METHODS: We applied the European (European Association for the Study of the Liver [EASL] 2012), Asian-Pacific (Asian-Pacific Association for the Study of the Liver [APASL] 2012), American (American Association for the Study of Liver Diseases [AASLD] 2009), and United States Panel Algorithm (USPA 2008) criteria to 366 consecutive hepatitis B e antigen-negative patients with liver biopsy samples: EASL, ALT >laboratory-defined upper limit of normal (ULN) and HBV DNA ≥2000 IU/mL (n = 171); APASL, ALT >2-fold laboratory-defined ULN and HBV DNA ≥2000 IU/mL (n = 87); AASLD, ALT >2-fold the updated ULN (0.5-fold ULN [corresponding to ≤19 U/L] for women and 0.75-fold the ULN [corresponding to ≤30 U/L] for men) and HBV DNA ≥20,000 IU/mL (n = 53); and USPA, ALT >updated ULN (>0.5-fold ULN for women and >0.75-fold ULN for men) and HBV DNA ≥2000 IU/mL (n = 173). RESULTS: Overall, 113 patients (30.9%) had ≥F2 fibrosis, which was more frequent among patients who fulfilled any guideline criteria (45.7% vs 17.9% for those who did not fulfill any criteria, P < .0001). In applying the EASL, AASLD, APASL, and USPA criteria, sensitivity and specificity values for detection of ≥F2 fibrosis were 45.6%, 58.5%, 56.3%, and 45.7% (P = .145) and 82.1%, 73.8%, 77.1%, and 82.4% (P = .366), respectively. The EASL criteria (area under the receiver operating characteristic [AUROC] curve, 0.66; 95% confidence interval [CI], 0.61-0.71) and USPA criteria (AUROC, 0.66; 95% CI, 0.58-0.73) performed better than APASL (AUROC, 0.64; 95% CI, 0.59-0.69; P = .421) and significantly better than the AASLD criteria (AUROC, 0.59; 95% CI, 0.54-0.64; P = .013). CONCLUSIONS: In hepatitis B e antigen-negative patients with chronic hepatitis, the EASL, AASLD, APASL, and USPA criteria identify patients with ≥F2 fibrosis with low levels of accuracy. However, the EASL and USPA criteria are the most accurate for identification of these patients.

The Efficacy of Manual Therapy and Pressure Biofeedback-Guided Deep Cervical Flexor Muscle Strength Training on Pain and Functional Limitations in Individuals with Cervicogenic Headaches: A Randomized Comparative Study.

Objective: This study aimed to compare the efficacy of manual therapy and pressure biofeedback-guided DCFM strength training on pain intensity and functional limitations in individuals with CGH. Trial Design. A double-blinded, two-arm parallel group randomized comparative design. Methods: After applying the eligibility criteria, sixty out of eighty-nine CGH patients were recruited from King Saud University Medical Center in Riyadh and randomly allocated to intervention groups using simple random sampling. Group 1 underwent pressure biofeedback-guided DCFM strength training and conventional treatment, while Group 2 received manual therapy and conventional treatment for three consecutive weeks. The main outcome measures were scores on the visual analog scale (VAS) and the headache disability index (HDI). One assessor and two physical therapists were blinded to group allocation. Results: Sixty out of eighty participants aged 29-40 years were randomized into intervention groups (n = 30/group; age (mean ± standard deviation): group 1 = 35.0 ± 2.82; group 2 = 34.87 ± 2.60), and their data were analyzed. A significant improvement (95% CI, p < 0.05) was observed within each group when comparing the VAS and HDI scores between baseline and postintervention. In contrast, between-group comparisons for the outcome score of VAS and HDI revealed nonsignificant differences in the first, second, and third weeks after intervention, except for the VAS score, which showed a significant difference in weeks 2 and 3 after intervention. Cohen's d-value indicated that the intervention effect size for reducing pain was larger in group 1 than in group 2 at weeks 2 and 3. Conclusion: Compared with manual therapy, pressure biofeedback-guided DCFM strength training showed a greater reduction in pain intensity (assessed using the VAS) at weeks two and three. However, both treatments were equally effective in lowering headache-related functional limitations in patients with CGH. This trial is registered with ClinicalTrial.gov PRS (Identifier ID: NCT05692232).

Characterization and in-vitro Alzheimer's properties of exopolysaccharide from Bacillus maritimus MSM1.

Four bacterial isolates were obtained from marine sediments collected from Sahl Hashish, Hurghada Red Sea, Egypt. This study was designed to search for promising anti-Alzheimer natural polysaccharide; therefore, four isolates were screened for exopolysaccharides (EPSs) production and acetylcholinesterase inhibition. The isolate S16 provided the highest EPS yield (7.51 g/L) and acetylcholinesterase inhibition. It was identified morphologically and genetically using 16S rRNA gene sequence analysis as Bacillus maritimus. A Physicochemical analysis of S16 exopolysaccharide (BMEPS) was estimated, which pointed to the presence of uronic acid and sulfate (24.7% and 18.3%, respectively). HPLC analysis indicated that mannuronic acid, glucuronic acid, glucose, and mannose are presented in a molar ratio of 0.8:1.0:2.8:2.3, respectively. Furthermore, FT-IR revealed an abundance of ß-configurations. The GPC estimated the average molecular weight (Mw) as 4.31 × 104 g/mol. BMEPS inhibited AChE (IC50; 691.77 ± 8.65 µg/ ml), BChE (IC50; 288.27 ± 10.50 µg/ ml), and tyrosinase (IC50; 3.34 ± 0.09, 14.00 ± 0.14, and 22.96 ± 1.23 µg/ ml during incubation durations of 10, 20, and 40 min). It also demonstrated a selective anti-inflammatory action against COX-2 rather than COX-1. Moreover, BMEPS exhibited antioxidant capabilities as free radical and oxygen reactive species (ROS) scavenger, metal chelator, reductant agent, and lipid peroxidation suppressor. These activities are due to the distinct chemical composition. The findings of this study indicate that BMEPS could be considered as promising anti-disease Alzheimer's (AD) material in an in-vitro model, which qualifies it for advanced in-vivo studies in the discovery of alternative Alzheimer's treatment.

Characterization of biologically active exopolysaccharide produced by Streptomyces sp. NRCG4 and its anti-Alzheimer efficacy: in-vitro targets.

BACKGROUND: Exopolysaccharides are extremely powerful molecules with a wide range of uses in pharmaceuticals due to their structural and compositional complexity. Marine microorganisms often produce bioactive substances with novel functions and structures because of their special living conditions. Polysaccharides from marine microorganisms are of interest to new drug discovery. RESULTS: The current research focused on the isolation of bacteria from Red Sea, Egypt, that have the ability to produce a new natural exopolysaccharide in order to be examined in treating Alzheimer's illness to obviate side effects of synthetic drugs. Properties of exopolysaccharide (EPS) produced by an isolated Streptomyces strain were investigated for its capability to play as anti-Alzheimer. This strain was identified morphologically, physiologically, and biochemically and actually was confirmed by molecularly 16S rRNA analysis as Streptomyces sp. NRCG4 with accession number MK850242. The produced EPS was fractionated by precipitation 1:4 volumes of chilled ethanol and the third major fraction (1:3) listed as NRCG4, and then the functional groups, MW, and chemical evaluation have been detected via Fourier-transform infrared (FTIR), high-performance gel permeation chromatography (HPGPC), and high-performance liquid chromatography (HPLC). The findings showed that NRCG4 was an acidic EPS composed of mannuronic acid, glucose, mannose, and rhamnose in a molar ratio of 1.2:1.5:2.8:1.0, respectively. NRCG4 Mw was determined to be 4.25 × 105 gmol-1 and the Mn to be 1.97 × 105 gmol-1. Also, the NRCG4 included uronic acid (16.0%) and sulfate (0.0%), but no protein was found. In addition, antioxidant and anti-inflammation activity was measured through various methods. This study confirmed that NRCG4 exopolysaccharide exerted anti-Alzheimer's characters via inhibition of cholinesterase and tyrosinase as well as anti-inflammatory and antioxidant abilities. Additionally, it occurred a potential role in the suppression of Alzheimer's disease risk factors through its antioxidant (metal chelation, radical scavenging capability), anti-tyrosinase and anti-inflammatory characteristics. The anti-Alzheimer's disease efficacy of NRCG4 exopolysaccharide may be assigned to its unique determined chemical composition. CONCLUSIONS: The present study highlighted those exopolysaccharides could be harnessed to improve pharmaceutical industry (anti-Alzheimer, anti-tyrosinase, anti-inflammatory, and antioxidant agents).

Effect of blood flow restriction as a stand-alone treatment on muscle strength, dynamic balance, and physical function in female patients with chronic ankle instability.

BACKGROUND: Blood Flow Restriction (BFR) training has gained popularity as a novel training strategy in athletes and rehabilitation settings in recent years. OBJECTIVE: To investigate whether BFR as a stand-alone treatment would affect muscle strength, dynamic balance, and physical function in female patients with chronic ankle instability (CAI). METHODS: Thirty-nine patients with CAI were randomly allocated into 1 of 3 groups: BFR as a stand-alone (BFR) group, BFR with rehabilitation (BFR+R) group, and rehabilitation (R) group. All groups trained 3 times per week for 4 weeks. One week before and after the intervention, strength of muscles around ankle joint, 3 dynamic balance indices: Overall Stability Index, Anterior-Posterior Stability Index, and Medial-Lateral Stability Index, and physical function were assessed via an isokinetic dynamometer, the Biodex Balance System, and the Foot and Ankle Disability Index, respectively. RESULTS: The strength of muscles around ankle and dynamic balance indices improved significantly in BFR + R and R groups (P < .006), but not in BFR group (P > .006). All dynamic balance indices showed improvement in BFR + R and R groups except the Medial-Lateral Stability Index (P > .006). Foot and Ankle Disability Index increased significantly in BFR + R and R groups (P < .006), however; no improvement occurred in BFR group (P > .006). CONCLUSIONS: The BFR as a stand-alone treatment hasn't the ability to improve the strength of muscles around the ankle, dynamic balance, and physical function in females with CAI compared to the BFR + R or the R program. In addition, the strength of muscles around the ankle correlated significantly with both dynamic balance and physical function in BFR + R and R groups.